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Sponsored by: |
Columbia University |
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Information provided by: | Columbia University |
ClinicalTrials.gov Identifier: | NCT00869258 |
The purpose of this study is to determine whether an experimental drug combination consisting of Gemzar®, Taxotere®, and Xeloda®, (called GTX) when followed by radiation therapy plus low-dose Gemzar, is safe and effective in treating advanced pancreatic cancer and to study and enhance the utility of PET scans in the evaluation of patients with pancreatic cancer.
Condition | Intervention | Phase |
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Pancreatic Cancer Stage IVA |
Drug: Gemcitabine, docetaxel, and capecitabine Radiation: Radiation therapy with gemcitabine |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study |
Official Title: | Phase II Study for Inoperable Non-Metastatic Pancreatic Cancer (Stage IVA) With Neoadjuvant Gemzar, Taxotere and Xeloda (GTX), and Radiation With Gemzar |
Estimated Enrollment: | 35 |
Study Start Date: | June 2005 |
Estimated Study Completion Date: | December 2010 |
Estimated Primary Completion Date: | December 2010 (Final data collection date for primary outcome measure) |
The evolution of our regimen, consisting of Gemzar, Taxotere and Xeloda (oral 5FU) (GTX), was carefully developed over the past three years from laboratory and clinical work. Initially, in collaboration with Dr. William Sherman of the Division of Medical Oncology we assessed the clinical effects of two agents, Gemzar and Taxotere in pancreatic cancer patients. In our in vitro studies we found that as single agents these drugs (Gemzar and Taxotere) were minimally effective against pancreatic carcinoma lines, which expressed mutant p53 and activated mutated ras. Activated or mutant ras is found in approximately 95% of all pancreatic carcinomas. However, when the agents were added together in tissue culture experiments we found that their activity was additive. The clinical study performed at Columbia Presbyterian Medical Center demonstrated a 27% objective response rate by CT scan including one complete response with intent to treat analysis of all 15 patients within the study. The majority of these patients had metastatic liver disease and a minority had inoperable pancreatic carcinoma without liver metastases. Though this was a small single arm, single institution study it did suggest a trend towards improved responses in patients with this disease when these two agents were combined. In addition, valuable lessons were learned from the in vitro work with Gemzar and Taxotere. Importantly, we found that this combination was equally toxic to mutant and wild type p53 pancreatic cancer cells, as well as to cells with mutant ras. Also, docetaxel pharmacokinetics are more favorable and have distinct advantages over the use of the other taxane known as paclitaxel. They are the following: 1) Taxotere enters tumor cells more efficiently than paclitaxel because it is more lipophilic; 2) Taxotere is not pumped out by the cell by P-glycoprotein as efficiently as paclitaxel; 3) Taxotere' half life was significantly longer than that of paclitaxel such that a 60 minute infusion of Taxotere gives you approximate pharmacokinetics as paclitaxel when administered as a 24 hour continuous infusion. These laboratory studies from the literature formed the rationale for our use of Taxotere (docetaxel) instead of paclitaxel.
After our initial clinical and laboratory study we went back to the laboratory to investigate further some of the properties of Gemcitabine, Taxotere added to Xeloda (5-DFUR) in vitro to maximize biochemical synergy and to minimize toxicity. We found important characteristics of these drug combinations against pancreatic cancer cells that have been synthesized into the current protocol. We found that there was sequence specificity for these drugs in that 5-DFUR should precede Gemzar by 72 to 96 hours and Gemzar should be added before Taxotere to achieve maximum synergy. Taxotere cytotoxicity was dose dependent up to 20 nM but then no further cell kill was obtained past that point. This would mean that one would not need to use high dose Taxotere in a regimen because it would be doubtful whether increased doses would obtain further cell kill in a linear scale.
We investigated many different combinations of these 3 agents in the laboratory to determine the best combination to achieve biochemical synergy while decreasing the concentration of each drug and not lose anti-tumor effect so as to decrease toxicity to patients.
Ages Eligible for Study: | 18 Years to 70 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Clinical Parameters
Contact: Vilma Rosario | 212-305-2666 | vr2222@columbia.edu |
Contact: Dawn Tsushima, RN | 212-305-1921 | dt2288@columbia.edu |
United States, New York | |
Columbia University Medical Center | Recruiting |
New York, New York, United States, 10032 | |
Contact: Vilma Rosario 212-305-2666 vr2222@columbia.edu |
Principal Investigator: | Robert L Fine, MD | Columbia University Medical Center |
Responsible Party: | Columbia University Medical Center ( Robert L. Fine M.D. ) |
Study ID Numbers: | GTX IVA, AAAB8630 |
Study First Received: | March 23, 2009 |
Last Updated: | April 20, 2009 |
ClinicalTrials.gov Identifier: | NCT00869258 History of Changes |
Health Authority: | United States: Institutional Review Board |
Antimetabolites Capecitabine Digestive System Neoplasms Immunologic Factors Pancreatic Neoplasms Endocrine System Diseases Immunosuppressive Agents Antiviral Agents |
Docetaxel Digestive System Diseases Radiation-Sensitizing Agents Gastrointestinal Neoplasms Pancreatic Diseases Endocrinopathy Gemcitabine Endocrine Gland Neoplasms |
Antimetabolites Anti-Infective Agents Capecitabine Digestive System Neoplasms Antimetabolites, Antineoplastic Immunologic Factors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Pancreatic Neoplasms Physiological Effects of Drugs Endocrine System Diseases Enzyme Inhibitors |
Immunosuppressive Agents Antiviral Agents Pharmacologic Actions Docetaxel Neoplasms Neoplasms by Site Digestive System Diseases Radiation-Sensitizing Agents Therapeutic Uses Pancreatic Diseases Gemcitabine Endocrine Gland Neoplasms |